Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Colorectal adenomas (CRAs) are the precursors of CRCs, but most CRAs do not progress to CRCs. Advanced CRAs, those CRAs most likely to progress, are highlighted in this Colon Cancer Prevention Program Project (CCPPP). Most CRAs are amenable to endoscopic polypectomy. Recurrent CRAs develop at a rate of 10-15% per year in patients with previous CRAs and serve as endpoints in CRC chemoprevention trials. CRA recurrence trials of a wheat bran fiber (WBF) supplement and ursodeoxychclic acid (UDCA) were completed in earlier CCPPP grants. The current is a placebo-controlled factorial-design, CRA recurrence trial of celecoxib and selenium (Cel/Sel), administered individually and together, to 1600 participants after a recent CRA polypectomy. Celecoxib, a selective cyclooxygenase (COX)- 2 inhibitor, is hypothesized to have less toxicity than aspirin with equivalent anti-neop!astic efficacy. Selenium supplementation has been shown to protect against CRC and prevalent CRAs as secondary but not primary trial endpoints. Cel/Sel randomization is stratified for concomitant low-dose aspirin (<81 mg daily) therapy RA recurrence rates by intervention group will be determined at endpoint colonoscopies performed 3 to 5 years after baseline. Cel/Sel randomization will be completed by early 2006. Resources, including hose from the WBF and UDCA trials, are essential for the conduct of CCPPP; they include clinical and risk factor data, baseline and recurrent CRA tissue, and archived plasma and DNA. By the completion of randomization of Cel/Sel trial participants in early 2006, baseline data from = 4,300 CRA patients will be available. In addition to individual effects of celecoxib and selenium, exploratory analyses of their nteraction will be conducted. As secondary objectives, the influence of single nucleotide polymorphism variations will be analyzed in six genes for which there is evidence of genotypic effect modification of the celecoxib, aspirin or selenium interventions, or their toxicities: ornithine decarboxylase, cytochrome P450 209. UDP-glucuronosyltransferase 1A6 and the GPx-1, GPx-2 and Sep15 selenoprotein genes.